Caspase-1 activity affects AIM2 speck formation/stability through a negative feedback loop.

Détails

Ressource 1Télécharger: fcimb-03-00014.pdf (2160.91 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_1245AFD27327
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Caspase-1 activity affects AIM2 speck formation/stability through a negative feedback loop.
Périodique
Frontiers in Cellular and Infection Microbiology
Auteur(s)
Juruj C., Lelogeais V., Pierini R., Perret M., Py B.F., Jamilloux Y., Broz P., Ader F., Faure M., Henry T.
ISSN
2235-2988 (Print)
ISSN-L
2235-2988
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
3
Pages
14
Langue
anglais
Résumé
The inflammasome is an innate immune signaling platform leading to caspase-1 activation, maturation of pro-inflammatory cytokines and cell death. Recognition of DNA within the host cytosol induces the formation of a large complex composed of the AIM2 receptor, the ASC adaptor and the caspase-1 effector. Francisella tularensis, the agent of tularemia, replicates within the host cytosol. The macrophage cytosolic surveillance system detects Francisella through the AIM2 inflammasome. Upon Francisella novicida infection, we observed a faster kinetics of AIM2 speck formation in ASC(KO) and Casp1(KO) as compared to WT macrophages. This observation was validated by a biochemical approach thus demonstrating for the first time the existence of a negative feedback loop controlled by ASC/caspase-1 that regulates AIM2 complex formation/stability. This regulatory mechanism acted before pyroptosis and required caspase-1 catalytic activity. Our data suggest that sublytic caspase-1 activity could delay the formation of stable AIM2 speck, an inflammasome complex associated with cell death.

Mots-clé
Animals, Apoptosis Regulatory Proteins, CARD Signaling Adaptor Proteins, Caspase 1/genetics, Caspase 1/metabolism, Cell Death, Cell Line, Cytoskeletal Proteins/genetics, DNA-Binding Proteins, Feedback, Francisella tularensis/immunology, Gene Deletion, Humans, Macrophages/immunology, Macrophages/microbiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins/metabolism, AIM2, Francisella tularensis, caspase-1, inflammasome, regulation
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/10/2017 11:05
Dernière modification de la notice
20/08/2019 13:40
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